Functions of SWAP-70 in B-cell Activation Signaling pathways that activate B lymphocytes and induce nuclear processes like immunoglobulin (Ig) heavy chain class switching, DNA repair, and DNA replication are incompletely understood. We have identified and characterized a novel phosphoprotein, SWAP-70, that is specifically expressed in activated B-cells and in mast cells. SWAP-70 has hallmarks of signaling proteins, translocates between cytoplasm and nucleus, interacts with DNA repair proteins in the nucleus, and associates with the B-cell antigen receptor. Our preliminary analysis of a mouse deficient in SWAP70-/- indicates a requirement for SWAP-70 in CD4O-triggered proliferation and Ig class switching, and for survival after gamma-irradiation. Thus, the central hypothesis in this application suggests an important contribution by protein SWAP-70 in B-cell activation. The specific aims of this application are to understand the roles of SWAP-70 in proliferation, Ig class switching, DNA repair, and apoptosis in B-cells. B-cell activation is key to the immune response and, if improperly controlled, at the heart of several human immune system diseases. Therefore, the analysis of SWAP-70 in B-cell activation is likely to help in our understanding of normal B-cell function as well as of immune deficiencies, B-cell malignancies, autoimmunity, and allergy.